Open Access

ARTICLE

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (DLAT) as a novel prognostic biomarker in pan-cancer and glioma

HUI ZHOU^#, ZHENGYU YU^#, JING XU, ZHONGWANG WANG, YALI TAO, JINJIN WANG, PEIPEI YANG, JINRONG YANG^*, TING NIU^*
Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
* Address correspondence to: Jinrong Yang, yangjinrong@wchscu.cn; Ting Niu, niuting@wchscu.cn
# These authors have contributed equally to this work and share the first authorship

Oncology Research https://doi.org/10.32604/or.2024.048138

Received 28 November 2023; Accepted 21 February 2024; Published online 10 April 2024

Abstract

Background: Dihydrolipoamide S-acetyltransferase (DLAT) is a subunit of the pyruvate dehydrogenase complex (PDC), a rate-limiting enzyme complex, that can participate in either glycolysis or the tricarboxylic acid cycle (TCA). However, the pathogenesis is not fully understood. We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors, and to investigate its function in patients’ prognosis and immunotherapy. Methods: The differential expression, diagnosis, prognosis, genetic and epigenetic alterations, tumor microenvironment, stemness, immune infiltration cells, function enrichment, single-cell analysis, and drug response across cancers were conducted based on multiple computational tools. Additionally, we validated its carcinogenic effect and possible mechanism in glioma cells. Results: We exhibited that DLAT expression was increased in most tumors, especially in glioma, and affected the survival of tumor patients. DLAT was related to RNA modification genes, DNA methylation, immune infiltration, and immune infiltration cells, including CD4+ T cells, CD8+ T cells, Tregs, and cancer-associated fibroblasts. Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis, inflammation, and stemness. Enrichment analysis revealed that DLAT might take part in the cell cycle pathway. Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds, including PI3Kβ inhibitors, PKC inhibitors, HSP90 inhibitors, and MEK inhibitors. In addition, glioma cells with DLAT silence inhibited proliferation, migration, and invasion ability, and promoted cell apoptosis. Conclusion: We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors, and its possible functions and mechanisms. DLAT is a potential diagnostic, prognostic, and immunotherapeutic biomarker for cancer patients.

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Graphical Abstract

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Keywords

DLAT, Glioma, Prognostic, Immunological

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